• Archives of Pharmacal Research
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• v.25 no.5
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• pp.718-723
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• 2002

CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin) is a recently-developed synthetic camptothecin analogue and currently under clinical development by Chong Kun Dang Pharm (Seoul, Korea). CKD-602 showed potent topoisomerase inhibitory activity in vitro and broad antitumor activity against various human tumor cells in vitro and in vivo in animal models. This study describes the pharmacodynamics of the immediate and delayed cytotoxicity induced by CKD-602 in a human colorectal adenocarcinoma cell line, HT-29, and its intracellular drug accumulation by HPLC. The present study was designed to address whether the higher activity of CKD-602 with prolonged exposure is due to delayed exhibition of cytotoxicity and/or an accumulation of anti proliferative effect on continuous drug exposure. The drug uptake study was performed to determine whether the delayed cytotoxicity is due to a slow drug accumulation in cells. CKD-602 produced a cytotoxicity that was exhibited immediately after treatment (immediate effect) and after treatment had been terminated (delayed effect). Both the immediate and delayed effects of CKD-602 showed a time dependent decrease in 4IC_{50}$ values. Drug uptake was biphasic and the second equilibrium level was obtained as early as at 24hr, indicating that the cumulative and delayed antitumor effects of CKD-602 were not due to slow drug uptake. On the other hand, CKD-602 treatment was sufficient to induce delayed cytotoxicity after 4hr, however, longer treatment (＞24hr) enhanced its cytotoxicity due to the intracellular accumulation of the drug, which requires 24hr to reach maximum equilibrium concentration. In addition, $C^n$$\times$T=h analysis (n=0.481) indicated that increased exposure times may contribute more to the overall antitumor activity of CKD-602 than drug concentration. Additional studies to determine the details of the intracellular uptake kinetics (e.g., concentration dependency and retention studies) are needed in order to identify the optimal treatment schedules for the successful clinical development of CKD-602.

• The Journal of Pediatrics of Korean Medicine
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• v.28 no.2
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• pp.56-71
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• 2014

Objectives In this study, the author tried to investigate whether piryongbang-gamgil-tang (PGGT) significantly affect in vitro airway mucin secretion, PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production / gene expression from human airway epithelial cells and increase in airway epithelial mucosubstances and hyperplasia of tracheal goblet cells of rats. Materials and Methods For in vitro experiment, confluent RTSE cells were chased for 30 min in the presence of PGGT to assess the effect of PGGT on mucin secretion by enzyme-linked immunosorbent assay (ELISA). Also, effect of PGGT on PMA- or EGFor TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of PGGT and treated with PMA (10 ng/ml) or EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24 hrs, to assess both effect of PGGT on PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production by ELISA and gene expression by reverse transcription-polymerase chain reaction (RT-PCR). For in vivo experiment, the author induced hypersecretion of airway mucus and goblet cell hyperplasia by exposure of rats to $SO_2$ during 3 weeks. Effect of orally-administered PGGT during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats and hyperplasia of goblet cells were assesed by using histopathological analysis after staining the epithelial tissue with alcian blue. Possible cytotoxicities of PGGT in vitro were assessed by examining LDH release from RTSE cells and the rate of survival and proliferation of NCI-H292 cells. In vivo liver and kidney toxicities of PGGT were evaluated by measuring serum GOT/GPT activities and serum BUN/creatinine concentrations of rats after administering PGGT orally. Results (1) PGGT did not affect in vitro mucin secretion from cultured RTSE cells. (2) PGGT significantly inhibited PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions and the expression levels of MUC5AC mRNA from NCI-H292 cells. (3) PGGT decreased the amount of intraepithelial mucosubstances and showed the tendency of expectorating airway mucus already produced. (4) PGGT increased LDH release from RTSE cells. However, PGGT did not show in vivo liver and kidney toxicities and cytotoxicity to NCI-H292 cells. Conclusion The result from this study suggests that PGGT can regulate the production and gene expression of airway mucin observed in diverse respiratory diseases accompanied by mucus hypersecretion and do not show in vivo toxicity to liver and kidney functions after oral administration. Effect of PGGT with their components should be further studied using animal experimental models that reflect the diverse pathophysiology of respiratory diseases through future investigations.

• The Korean Journal of Pain
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• v.24 no.4
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• pp.191-198
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• 2011

Background: Postlaminectomy peridural fibrosis is inevitable. Some studies have compared and identified the effects of high molecular weight hyaluronic acids (HMWHA) and low molecular weight hyaluronic acids (LMWHA) on peridural fibrosis in postlaminectomy animal models. However, no studies have been found that compare pain behaviors between hyaluronic acids or among hyaluronic acids and other solid materials. The purpose of this study was to examine the correlation between pain-related behaviors and histopathologic changes in laminectomized rats using various peridurally administered materials. Methods: Forty male Sprague-Dawley rats, laminectomized at the L5 and L6 levels, were divided into four groups: group C, laminectomy only; group L, laminectomy and LMWHA application; group H, laminectomy and HMWHA application; group F, laminectomy and fat interposition. Pain behaviors were checked before, 3 days, 1 week, and 3 weeks after surgery. Histopathological changes were checked at the L5 level 3 weeks after the surgery. Results: The 50% withdrawal thresholds in groups L and H were higher than that in groups C and F three days after laminectomy (P < 0.05). The paw withdrawal time did not change among the groups and in each group during the study period. Peridural fibrosis in group F was significantly lower than in the other groups (P < 0.05). Conclusions: Hyaluronic acids significantly reduced mechanical allodynia but not thermal hyperalgesia. Peridural fibrosis did not show any correlation with pain behaviors. There have been limited studies on the correlation between peridural fibrosis and pain behavioral change, which should be verified by further studies.

• Journal of Microbiology and Biotechnology
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• v.30 no.11
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• pp.1614-1625
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• 2020

A number of species of the genus Trichilia (Meliaceae) exhibit anti-inflammatory effects. However, the effect of Trichilia martiana C. DC. (TM) on lipopolysaccharide (LPS)-induced inflammation has not, to the best of our knowledge, yet been determined. Therefore, in the present study, the antiinflammatory effect of TM on LPS-stimulated RAW264.7 macrophages was evaluated. The ethanol extract of TM (TMEE) significantly inhibited LPS-induced nitric oxide (NO), prostaglandin 2 (PGE₂), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). TMEE also reduced the levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and IL-6. The upregulation of mitogen-activated protein kinases (MAPKs) and NF-κB activation was revealed to be downregulated following TMEE pretreatment. Furthermore, TMEE was indicated to lead to the nucleus translocation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1). In H292 airway epithelial cells, the pretreatment of TMEE significantly downregulated the production of LPS-stimulated IL-1β, and TMEE was indicated to increase the expression of HO-1. In animal models exhibiting LPS-induced acute lung injury (ALI), treatment with TMEE reduced the levels of macrophages influx and TNF-α production in the bronchoalveolar lavage fluid (BALF) of ALI mice. Additionally, TMEE significantly downregulated the activation of ERK, JNK and IκB, and upregulated the expression of HO-1 in the lungs of ALI mice. In conclusion, the results of the current study demonstrated that TMEE could exert a regulatory role in the prevention or treatment of the endotoxin-mediated inflammatory response.

• Journal of the Korean Data and Information Science Society
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• v.26 no.6
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• pp.1409-1416
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• 2015

The change of temperature influences on the various aspect, especially human health, plant and animal's growth, economics, industry, and culture of the country. In this article, the autoregressive error (ARE) model has been considered for analyzing the monthly temperature data at the Suwon monitoring site in Korea. In the ARE model, five meteorological variables, four greenhouse gas variables and five pollution variables are used as the explanatory variables for the temperature data set. The five meteorological variables are wind speed, rainfall, radiation, amount of cloud, and relative humidity. The four greenhouse gas variables are carbon dioxide ($CO_2$), methane ($CH_4$), nitrous oxide ($N_2O$), and chlorofluorocarbon ($CFC_{11}$). And the five air pollution explanatory variables are particulate matter ($PM_{10}$), sulfur dioxide ($SO_2$), nitrogen dioxide ($NO_2$), ozone ($O_3$), and carbon monoxide (CO). Among five meteorological variables, radiation, amount of cloud, and wind speed are more influence on the temperature. The radiation influences during spring, summer and fall, whereas wind speed influences for the winter time. Also, among four greenhouse gas variables and five pollution variables, chlorofluorocarbon, methane, and ozone are more influence on the temperature. The monthly ARE model explained about 43-69% for describing the temperature.

• The korean journal of orthodontics
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• v.20 no.3 s.32
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• pp.447-462
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• 1990

The objective of this experiment is to observe structural differences in the othodontic movement of vital (control group) and devitalized (experimental group) teeth in the mongrel dogs. The 5 utilized dogs in this experiment were approximately 1 year of age and their average weight was about 12 Kg. Endodontic therapy was performed on the 2nd premolars in upper & lower jaws of each animal under the general anesthesia by intravascular injection of 25mg/kg of pentobarbital sodium. The canals of the teeth were obturated by using gutta percha in conjunction with root canal sealer (AH26 Densply). One of the roots in the 2nd premolars was hemisected to make an extraction space for the devitalized teeth to be moved. The edgewise technique was employed for the movement of the teeth. Orthodontic models and intraoral roentgenograms were taken before and after orthodontic tooth movement. The open coil springs (.010 x .040) were used at interbraket space in order to provide equal forces (75gm) between the teeth in each arch wire. After 13 weeks of active orthodontic tooth movement, dogs were sacrified and the experimental results w ere examined through the intraoral radiography, microscopic examination and scanning electromicroscopic examination at the root sulfate. From the results of the study, the following conclusions may be drawn: The root resolution and cemental deposition were observed within the pressure and tension site in both group. 2. The root resorbed lacunae were observed in the cementum and/or into the dentin in both group. 3. The prominent osteoblastic activities were observed on the alveolar margin in the tension site in both group. 4. A few of blood vessels were observed in the pressure site, but also lots of blood vessels were observed in the tension site especially in the periphery of the alveolar bone in both group. 5. In the pressure site, resorbed lacunae were formed with deep and narrow cavity in the control group; the shallow and wide cavity in the experimental group. 6. In the pressure site, the repaired cementum or cementoid tissue was lined on cementum in the experimental group, but not in the control group. 7. There was no significant difference between external root resolution of endodontically and vital teeth when both were subjected to orthodontic forces.

• Journal of Periodontal and Implant Science
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• v.42 no.6
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• pp.204-211
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• 2012

Purpose: This study was performed to establish an experimental rabbit model for single-stage maxillary sinus augmentation with simultaneous implant placement. Methods: Twelve mature New Zealand white rabbits were used for the experiments. The rabbit maxillary sinuses were divided into 3 groups according to sinus augmentation materials: blood clot (BC), autogenous bone (AB), and bovine-derived hydroxyapatite (BHA). Small titanium implants were simultaneously placed in the animals during the sinus augmentation procedure. The rabbits were sacrificed 4 and 8 weeks after surgery and were observed histologically. Histomorphometric analyses using image analysis software were also performed to evaluate the parameters related to bone regeneration and implant-bone integration. Results: The BC group showed an evident collapse of the sinus membrane and limited new bone formation around the original sinus floor at 4 and 8 weeks. In the AB group, the sinus membrane was well retained above the implant apex, and new bone formation was significant at both examination periods. The BHA group also showed retention of the elevated sinus membrane above the screw apex and evident new bone formation at both points in time. The total area of the mineral component (TMA) in the area of interest and the bone-to-implant contact did not show any significant differences among all the groups. In the AB group, the TMA had significantly decreased from 4 to 8 weeks. Conclusions: Within the limits of this study, the rabbit sinus model showed satisfactory results in the comparison of different grafting conditions in single-stage sinus floor elevation with simultaneous implant placement. We found that the rabbit model was useful for maxillary sinus augmentation with simultaneous implant placement.

• Journal of Chest Surgery
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• v.40 no.1 s.270
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• pp.1-7
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• 2007

Backgound: It has been shown that the endothelium of cardiac valves and adjacent great vessels have a reduced immune reaction compared to other vessels. We investigated the clinical feasibility of using immunologically untreated xenogenic valves, in a pig-to-goat pulmonary valve conduit implantation model. Material and Method: Porcine pulmonary valve conduits were prepared without specific immunologic treatment and implanted into the right ventricular outflow tract of goats while undergoing cardiopulmonary bypass. Two goats each were assigned to the following observation time intervals: one day, one week, three months, six months and twelve months. Echo-cardiographic examinations were performed prior to sacrifice of the goat to evaluate pulmonary valve function. After the xenograft specimens were retrieved, histological changes were evaluated microscopically. Result: Ten of the twelve animals survived the predetermined observation time intervals. Aneurysmal dilatations, of the anterior wall of the implanted pulmonary artery, were observed at each of three and twelve month-survival animals. A variable degree of pulmonary valve regurgitation was observed on echocardiography. However, valve stenosis, thrombotic occlusion and vegetation were not seen. Microscopically, the nuclei of the donor tissue disappeared as a result of pyknosis and karyolysis; however the three components of the implanted xenografts (the pulmonary artery, the valve and the infundibulum) were gradually replaced by host cells over time, while maintaining their structural integrity. Conclusion: Immunologically untreated xenogenic pulmonary valve conduits were replaced by host cells with few observed clinical problems in a pig to goat pulmonary valve implantation model. Therefore, they might be an alternative bioprosthesis option.

• Journal of Veterinary Clinics
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• v.24 no.3
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• pp.325-330
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• 2007

This study was to determine whether canine model which produce acute permanent joint instability in short period without postoperative exercise have a degenerative changes and also evaluated its suitability as an appropriate animal OA models. Ten skeletally mature beagle dogs underwent a unilateral surgical transection of the cranial cruciate ligament and, the medial collateral ligament as well as a medial meniscectomy. The contra-lateral joint was used as control. After 12 weeks, After 12 weeks, the amount of joint damage, inflammation and biochemical change of synovial fluid was evaluated. Histological analysis showed chondrocyte clone formation, hypertrophy of the cartilage and moderate loss of proteoglycans in the experimental joints compared to control joints. In addition, the synovial inflammation in the experimental joints was observed. Biochemical analysis of SF showed significantly increased MMP (matrix metalloproteinase) -2 and -9 in experimental joints compared to control joints. This canine OA model shows the characteristics of degenerative joint disease, and may have a advantages of reducing the time and cost because postoperative exercise is not needed in this OA model.

• Korean Journal of Medicinal Crop Science
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• v.26 no.4
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• pp.271-280
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• 2018

Background: Astragalus membranaceus is a well known oriental medicinal herb. The polysaccharides of the aboveground parts (AMA) and the radix (AMR) of A. membranaceus are the most important functional constituents. Methods and Results: The aim of this study was to determine the effects of AMA and AMR on the oxidative damage induced in the skeletal muscle of rats subjected to exhaustive exercise. Sprague-Dawley rats were randomly divided into exercise and non-exercise groups; in the groups receiving the test compounds, AMA and AMR were administered orally for 30 days. Skeletal muscle samples were collected from each rat after running to exhaustion on a treadmill to determine the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) and the concentation of malondialdehyde (MDA). The antioxidant enzyme activities of SOD and GSH-Px of skeletal muscle of AMA- and AMR-treated groups were significantly higher than those of the control and commercial sports drink (SPD)-treated groups in exhaustive exercise rats. In addition, MDA concentrations in the skeletal muscle of the AMA- and AMR-treated groups were significantly lower than those of the control and SPD-treated groups. In the present study, the effects of AMA and AMR on exercise endurance capacity were also evaluated in mice subjected to a swimming exercise test. AMA and AMR supplementation prolonged the swimming time of mice and enhanced exercise endurance capacity. AMA and AMR possess the ability to retard and lower the production of blood lactate, and prevent the decrease of serum blood glucose. Conclusions: These results showed that, AMR and AMA exerted beneficial effect in mice, increasing the activity of the antioxidant systems and inhibiting oxidative stress induced by exhaustive exercise. The compounds improved exercise performance and showed anti-fatigue effects against exhaustive exercise.